Cell surface glycoconjugates, especially glycosphingolipids and glycoproteins, are believed to regulate many of the steps in nervous system development and differentiation. Disturbances caused by genetic and environmental factors are therefore likely to be causes of many types of mental retardation but little is known of the mechanisms by which the amount or type of cell surface glycoconjugate is controlled. A major aim of this proposal is to use neuroblastoma and hybrid neurotumor cell lies, possessing adenylate cyclase-linked receptors for prostaglandins, enkephalins, serotonin, acetylcholine, etc., to test a hypothesis that certain glycosyltransferase activities can be activated in vivo by increased levels of cylic AMP/protein kinase activation and vice-versa. Attempts will be made to purify specific hexosaminyl- and galactosyl-transferase activities and demonstrate in vitro that they can be activated by cAMP-protein kinase-dependent phosphorylation mechanisms. Changes in cell surface glycoconjugates following receptor occupancy will be monitored by conventional labelling techniques ((3H) GlcN incorporation, galactose oxidase/NaB3H4 labelling, (125I) lectin and toxin binding etc.) together with newer techniques, (including high pressure liquid chromatography, hydrazinolysis and lectin affinity chromatography) for isolation and characterization of glycoconjugates. A second project will use oligodendroglioma and Schwannoma cell lines and isolated, cultured, lamb oligodendrocytes to continue studies on the hormonal induction of myelin-associated glycolipids, the role (if any) of neurotransmitter-adenylate cyclase systems in myelination and to test suspected hypomyelinating and demyelinating agents. A third project will investigate the role of lysosomal hydrolases in glycoconjugate regulation by focussing on alpha-L-fucosidase, its phosphorylation, and its receptor-mediated high affinity uptake by neural cells in culture.